US4865770A - Process for the optical resolution of 2-(6-methoxy-2-naphthyl)propionic acid - Google Patents
Process for the optical resolution of 2-(6-methoxy-2-naphthyl)propionic acid Download PDFInfo
- Publication number
- US4865770A US4865770A US07/209,291 US20929188A US4865770A US 4865770 A US4865770 A US 4865770A US 20929188 A US20929188 A US 20929188A US 4865770 A US4865770 A US 4865770A
- Authority
- US
- United States
- Prior art keywords
- naphthyl
- methoxy
- propionic acid
- ethylamine salt
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000003287 optical effect Effects 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 15
- CMWTZPSULFXXJA-UHFFFAOYSA-N 2-(6-methoxy-2-naphthalenyl)propanoic acid Chemical compound C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 150000003947 ethylamines Chemical class 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 7
- 238000010899 nucleation Methods 0.000 claims abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 34
- WGMXALZBTBYPQD-UHFFFAOYSA-N ethanamine;2-(6-methoxynaphthalen-2-yl)propanoic acid Chemical compound CCN.C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 WGMXALZBTBYPQD-UHFFFAOYSA-N 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 239000002244 precipitate Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 230000006340 racemization Effects 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 239000012452 mother liquor Substances 0.000 claims 2
- 150000007513 acids Chemical class 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 238000002407 reforming Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- RQBBFKINEJYDOB-UHFFFAOYSA-N acetic acid;acetonitrile Chemical compound CC#N.CC(O)=O RQBBFKINEJYDOB-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 101150108015 STR6 gene Proteins 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- -1 chloro ions Chemical class 0.000 description 1
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
Definitions
- the present invention relates to a process for the optical resolution of 2-(6-methoxy-2-naphthyl) propionic acid enantiomers.
- 2-(6-methoxy-2-naphthyl) propionic acid which is also known under the denomination of Naproxen, has been used in human therapy for a long time, due to its antiinflammatory properties.
- supersaturated solutions of 2-(6-methoxy-2-naphthyl) propionic acid can be obtained using as solvents acetone or methanol containing 4 to 20% of water. Particularly preferred is the use of acetone containing 15 to 18% of water.
- precipitation was observed at about 30°-35° C., whereas, in case of higher water percentages, precipitation will require lower temperatures.
- Such a method allows to separate the optically pure dextro salt, from which the acid can be obtained by treatment with a mineral acid.
- Acetone mother liquors were heated to about 45° C., added with 60 g of ( ⁇ )-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt and stirred till complete dissolution.
- Acetone mother liquors were added again with 60 g of ( ⁇ )-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt and heated to 45° C. till complete dissolution.
- (+)-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt After cooling to 35° C. and seeding with 1 g of (+)-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt, working was carried out as above described, to obtain again 60 g of (+)-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt.
- Cycles can be repeated for an undetermined number of times, carefully controlling volume, water percentages and concetrations of both ( ⁇ )-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt and (-)-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt so as to comply with saturation and supersaturation values, respectively of about 170 and 200 g. For this purpose, it is necessary to carefully analyze the optical quality of each crystallization crop and to calculate the effectively obtained amount of each enantiomer.
- Mother solution will be then added with amounts of racemate and possibly of optical enantiomer necessary to respect the initial balance.
- the suspension was cooled to ⁇ 30° C. and filtered, the precipitate was washed with water till absence of chloro ions. 180 g of a white product having almost theorical optical activity was obtained.
- Mother liquors had a volume of 4.000-4.200 ml and K.F. 5.5-6%; 75 g of ( ⁇ )-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt was added thereto under mild reflux. After cooling to about 45° C., seeding was carried out with 2 g of (+)-2-(6-methoxy-2-naphthyl) propionic acid ethylamine salt, slowly stirring for 2 hours, letting temperature decrease to about 35° C.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Luminescent Compositions (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21254/87A IT1222013B (it) | 1987-07-10 | 1987-07-10 | Processo di risoluzione ottica di acido 2 (6 metossi 2 naftil) propionico |
| IT21254A/87 | 1987-07-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US4865770A true US4865770A (en) | 1989-09-12 |
Family
ID=11179093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US07/209,291 Expired - Fee Related US4865770A (en) | 1987-07-10 | 1988-06-20 | Process for the optical resolution of 2-(6-methoxy-2-naphthyl)propionic acid |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4865770A (de) |
| EP (1) | EP0298395B1 (de) |
| JP (1) | JP2607131B2 (de) |
| AT (1) | ATE72224T1 (de) |
| CA (1) | CA1316938C (de) |
| DE (1) | DE3868159D1 (de) |
| ES (1) | ES2031957T3 (de) |
| GR (1) | GR3003748T3 (de) |
| IT (1) | IT1222013B (de) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5015764A (en) * | 1990-06-18 | 1991-05-14 | Ethyl Corporation | Preparation of optically active aliphatic carboxylic acids |
| US5097064A (en) * | 1989-09-05 | 1992-03-17 | Rhone-Poulenc Sante | Process for preparing optically active 2-arylpropionic acids |
| US5189208A (en) * | 1991-07-01 | 1993-02-23 | Ethyl Corporation | Ibuprofen resolution |
| US5191112A (en) * | 1989-10-17 | 1993-03-02 | Nissan Chemical Industries, Ltd. | Process for optical resolution of (±)-2-(3-benzoyl)-phenylpropionic acid |
| US5196575A (en) * | 1992-02-19 | 1993-03-23 | Hoechst Celanese Corp. | Supercritical separation of isomers of functional organic compounds at moderate conditions |
| US5248813A (en) * | 1992-10-14 | 1993-09-28 | Ethyl Corporation | Enantiomeric resolution |
| US5256816A (en) * | 1992-10-14 | 1993-10-26 | Ethyl Corporation | Enantiomeric resolution |
| US5260482A (en) * | 1992-10-14 | 1993-11-09 | Ethyl Corporation | Enantiomeric resolution |
| US5278337A (en) * | 1992-10-14 | 1994-01-11 | Ethyl Corporation | Enantiomeric resolution of aryl-substituted aliphatic carboxylic acids |
| US5442117A (en) * | 1993-12-13 | 1995-08-15 | Albemarle Corporation | Enantiomeric resolution |
| US5696165A (en) * | 1991-05-13 | 1997-12-09 | The Boots Company Plc | Composition of s(-) sodium ibuprofen |
| US6436990B1 (en) | 1999-10-27 | 2002-08-20 | Nobex Corporation | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6525098B1 (en) | 1999-10-27 | 2003-02-25 | Nobex Corporation | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6552078B2 (en) | 1999-10-27 | 2003-04-22 | Nobex Corp | 6-methoxy-2-naphthylacetic acid prodrugs |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5302751A (en) * | 1992-01-21 | 1994-04-12 | Ethyl Corporation | Profen resolution |
| JP2560185B2 (ja) * | 1992-11-20 | 1996-12-04 | ボーグ・ワーナー・オートモーティブ株式会社 | 低騒音チエーン伝動装置 |
| DE19717429A1 (de) * | 1997-04-25 | 1998-12-24 | Bayer Ag | Herstellung enantiomerenreiner Biarylketocarbonsäuren |
| JP3226038B2 (ja) | 2000-03-15 | 2001-11-05 | 株式会社椿本チエイン | 低騒音型サイレントチェーン |
| DK2344435T3 (en) * | 2008-07-29 | 2016-04-18 | Poxel | Process for isolating enantiomeric components from enantiomeric mixtures by particle size controlled crystallization |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4376213A (en) * | 1981-03-06 | 1983-03-08 | Sumitomo Chemical Company, Limited | Method for optical resolution of 2-(4-chlorophenyl)-3-methylbutanoic acid |
| US4417070A (en) * | 1981-04-15 | 1983-11-22 | Nissan Chemical Industries, Ltd. | Process for preparing an optical active ester of naphthylpropionic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5965075A (ja) * | 1982-10-06 | 1984-04-13 | Nisshin Flour Milling Co Ltd | （±）−２−（６−メトキシ−２−ナフチル）プロピオン酸の光学分割法 |
| US4709082A (en) * | 1984-10-25 | 1987-11-24 | Nissan Chemical Industries, Ltd. | 2-phenylpropionic acid esters, method for optical resolution thereof and optically active substance thereof |
-
1987
- 1987-07-10 IT IT21254/87A patent/IT1222013B/it active
-
1988
- 1988-06-20 US US07/209,291 patent/US4865770A/en not_active Expired - Fee Related
- 1988-07-01 DE DE8888110557T patent/DE3868159D1/de not_active Expired - Lifetime
- 1988-07-01 ES ES198888110557T patent/ES2031957T3/es not_active Expired - Lifetime
- 1988-07-01 EP EP88110557A patent/EP0298395B1/de not_active Expired - Lifetime
- 1988-07-01 AT AT88110557T patent/ATE72224T1/de not_active IP Right Cessation
- 1988-07-05 JP JP63167630A patent/JP2607131B2/ja not_active Expired - Lifetime
- 1988-07-07 CA CA000571448A patent/CA1316938C/en not_active Expired - Fee Related
-
1992
- 1992-02-07 GR GR920400171T patent/GR3003748T3/el unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4376213A (en) * | 1981-03-06 | 1983-03-08 | Sumitomo Chemical Company, Limited | Method for optical resolution of 2-(4-chlorophenyl)-3-methylbutanoic acid |
| US4417070A (en) * | 1981-04-15 | 1983-11-22 | Nissan Chemical Industries, Ltd. | Process for preparing an optical active ester of naphthylpropionic acid |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5097064A (en) * | 1989-09-05 | 1992-03-17 | Rhone-Poulenc Sante | Process for preparing optically active 2-arylpropionic acids |
| US5191112A (en) * | 1989-10-17 | 1993-03-02 | Nissan Chemical Industries, Ltd. | Process for optical resolution of (±)-2-(3-benzoyl)-phenylpropionic acid |
| US5015764A (en) * | 1990-06-18 | 1991-05-14 | Ethyl Corporation | Preparation of optically active aliphatic carboxylic acids |
| US6525214B1 (en) | 1991-05-13 | 2003-02-25 | Bernard John Armitage | Therapeutic agent |
| US6242000B1 (en) | 1991-05-13 | 2001-06-05 | The Boots Company Plc | Composition of S−sodium ibuprofen |
| US5696165A (en) * | 1991-05-13 | 1997-12-09 | The Boots Company Plc | Composition of s(-) sodium ibuprofen |
| US5189208A (en) * | 1991-07-01 | 1993-02-23 | Ethyl Corporation | Ibuprofen resolution |
| US5196575A (en) * | 1992-02-19 | 1993-03-23 | Hoechst Celanese Corp. | Supercritical separation of isomers of functional organic compounds at moderate conditions |
| US5278337A (en) * | 1992-10-14 | 1994-01-11 | Ethyl Corporation | Enantiomeric resolution of aryl-substituted aliphatic carboxylic acids |
| US5260482A (en) * | 1992-10-14 | 1993-11-09 | Ethyl Corporation | Enantiomeric resolution |
| US5256816A (en) * | 1992-10-14 | 1993-10-26 | Ethyl Corporation | Enantiomeric resolution |
| US5248813A (en) * | 1992-10-14 | 1993-09-28 | Ethyl Corporation | Enantiomeric resolution |
| US5442117A (en) * | 1993-12-13 | 1995-08-15 | Albemarle Corporation | Enantiomeric resolution |
| US6436990B1 (en) | 1999-10-27 | 2002-08-20 | Nobex Corporation | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6525098B1 (en) | 1999-10-27 | 2003-02-25 | Nobex Corporation | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6552078B2 (en) | 1999-10-27 | 2003-04-22 | Nobex Corp | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6610739B2 (en) | 1999-10-27 | 2003-08-26 | Nobex Corporation | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6653348B2 (en) | 1999-10-27 | 2003-11-25 | Nobex Corporation | 6-methoxy-2-naphthylacetic acid prodrugs |
| US6713510B2 (en) | 1999-10-27 | 2004-03-30 | Nobex Corporation | 6-Methoxy-2-naphthylacetic acid prodrugs |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2031957T3 (es) | 1993-01-01 |
| JPH0219339A (ja) | 1990-01-23 |
| ATE72224T1 (de) | 1992-02-15 |
| EP0298395A1 (de) | 1989-01-11 |
| DE3868159D1 (de) | 1992-03-12 |
| IT8721254A0 (it) | 1987-07-10 |
| IT1222013B (it) | 1990-08-31 |
| CA1316938C (en) | 1993-04-27 |
| GR3003748T3 (de) | 1993-03-16 |
| EP0298395B1 (de) | 1992-01-29 |
| JP2607131B2 (ja) | 1997-05-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4865770A (en) | Process for the optical resolution of 2-(6-methoxy-2-naphthyl)propionic acid | |
| JP2875894B2 (ja) | イブプロフェンリシネートの生成及び分割 | |
| CA2150355C (en) | Process of resolving phenylpropionic acids using alpha-methylbenzylamine | |
| EP0325965B1 (de) | Verfahren zur optischen Spaltung einer rakemischen Säure | |
| US4546201A (en) | Process for the optical resolution of (±)2-(6'methoxy-2'-naphthyl)-propionic acid | |
| US4151198A (en) | Resolution of N-acyl-DL (+)-phenylalanines | |
| JP4257573B2 (ja) | Ｒ（＋）α−リポ酸の製造方法 | |
| EP0044984B1 (de) | Verfahren zur optischen Trennung von Mischungen aus d- und l-2-(6-Methoxy-2-naphthyl)-propionsäuren, das Cinchonidinsalz der d-2-(6-Methoxy-2-naphthyl)-propionsäure und Verfahren zu dessen Herstellung | |
| US4434107A (en) | Process for preparing an optically active p-hydroxyphenylglycine or a salt thereof | |
| US4340751A (en) | Method of optical resolution of (±)-2-amino-1-butanol and/or (±)-mandelic acid | |
| Hongo et al. | Asymmetric transformation of DL-p-hydroxyphenylglycine by a combination of preferential crystallization and simultaneous racemization of the o-toluenesulfonate. | |
| US5183922A (en) | Process for the optical resolution of threo-2-hydroxy-3-(2'-aminophenylthio)-3-(4"-methoxyphenyl)-propionic acid | |
| US4508919A (en) | Process for the preparation of optically active cyclopropane carboxylic acids | |
| US5097059A (en) | Resolution process of intermediates useful for the preparation of diltiazem | |
| EP0437566B1 (de) | Phenylglycinderivate | |
| US4824964A (en) | Method for preparing optically active N-acetylindoline-2-carboxylic acid | |
| US4285884A (en) | Process for resolution of racemic DL-α-aminocarboxylic acids | |
| KR100235374B1 (ko) | 2-아미노나프티리딘 유도체의 광학 이성질체 제조 방법 | |
| IE902360A1 (en) | Process for the resolution of threo-3-[(2-aminophenyl)-thio]-2-hydroxy-3-(4-Methoxy- phenyl) propionic acid | |
| US4925955A (en) | Resolution of (1S,4R)-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl) pyrano[3,4-B]indole-1-acetic acid using brucine | |
| US3174986A (en) | Process for resolving zinc racemic glutamate | |
| US5892093A (en) | Resolution | |
| CA1210014A (en) | Diastereomers of 1-ethyl-2-aminomethyl pyrrolidine | |
| US3481976A (en) | Process for optical resolution of calcium pantothenate | |
| JPS61501704A (ja) | 光学的活性フェニルアラニンおよびそれらのｎ−アシル誘導体並びにそれらの化合物の新規なジアステレオマ−塩の製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: INDUSTRIA CHIMICA PROFARMACO S.P.A., VIA A. DORIA, Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:PISELLI, FULVIO L.;REEL/FRAME:004935/0340 Effective date: 19880607 |
|
| FPAY | Fee payment |
Year of fee payment: 4 |
|
| AS | Assignment |
Owner name: CAMBREX ITALY S.R.L., ITALY Free format text: MERGER;ASSIGNOR:PROFARMACO NOBEL S.R.L.;REEL/FRAME:008178/0639 Effective date: 19950531 Owner name: PROFARMACO NOBEL S.R.L., ITALY Free format text: MERGER;ASSIGNOR:INDUSTRIA CHIMICA PROFARMACO S.P.A.;REEL/FRAME:008031/0871 Effective date: 19891222 Owner name: PROFARMACO S.R.L., ITALY Free format text: CHANGE OF NAME;ASSIGNOR:CAMBREX ITALY S.R.L.;REEL/FRAME:008178/0649 Effective date: 19950531 |
|
| FPAY | Fee payment |
Year of fee payment: 8 |
|
| REMI | Maintenance fee reminder mailed | ||
| LAPS | Lapse for failure to pay maintenance fees | ||
| FP | Lapsed due to failure to pay maintenance fee |
Effective date: 20010912 |
|
| STCH | Information on status: patent discontinuation |
Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362 |